Cervix
Benign / nonneoplastic lesions
Arias-Stella reaction

Author: Leonel Maldonado, M.D. (see Authors page)

Revised: 22 March 2017, last major update March 2017

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PubMed search: Arias Stella cervix

Cite this page: Arias-Stella reaction. PathologyOutlines.com website. http://pathologyoutlines.com/topic/cervixariasstella.html. Accessed March 27th, 2017.
Definition / General
  • First described in 1954 by Dr. Javier Arias-Stella (AMA Arch Pathol 1954;58:112)
  • Refers to nuclear changes in endocervical glands similar to those in endometrium commonly seen during pregnancy (10%) or postpartum
Essential Features
  • The main characteristic is cellular enlargement, mainly of the nucleus, to double or many times the normal size; without this feature, the phenomenon cannot be diagnosed
  • The cells have abundant clear or oxyphilic cytoplasm and large atypical, hyperchromatic and irregular nuclei with variable chromatin distribution
  • Associated with pregnancy (intrauterine or ectopic), oral contraceptive use or trophoblastic disease
Terminology
  • Also known as Arias-Stella phenomenon, effect or change
ICD-10 coding
  • N88.8: other specified noninflammatory disorders of cervix uteri
  • N88.9: noninflammatory disorder of cervix uteri, unspecified
Epidemiology
  • The Arias-Stella reaction occurs in the endocervix of pregnant women at a frequency that ranges between 9% and 37.5%
  • The Arias-Stella reaction is seen in women between 19 and 44 years of age
Sites
  • Affects glandular cells of the endometrium, but also of the endocervix and fallopian tube
  • Can also be seen in other areas or lesions, including endometriosis, endocervical polyps, vaginal adenosis, germinal inclusion cysts of the ovary, paraovarian and paratubal cysts and mucinous cystadenoma
Pathophysiology
  • In response to high levels of human chorionic gonadotropin and exposure to estrogens and progesterone stimulation, proliferative (estrogens) and secretory (progesterone) activity occur together, resulting in large, pleomorphic cells with large, hyperchromatic nuclei and prominent nucleoli
Etiology
  • Pregnancy and oral contraceptive use
Clinical Features
  • Almost always associated with pregnancy (either intrauterine or ectopic) or with trophoblastic disease; it rarely occurs secondary to hormone therapy, especially progestins
  • Arias-Stella reaction in the cervix can present as involvement of an endocervical polyp or as an incidental finding in cervical tissue obtained for other reasons
Case Reports
Treatment
  • Arias-Stella changes disappear after pregnancy
Gross Description
  • No mass lesions are grossly identified
Micro Description
  • Main characteristic is cellular enlargement, mainly of the nucleus, to double or many times the normal size; without this feature, the phenomenon cannot be diagnosed (Am J Surg Pathol 2004;28:608)
  • The glandular cells are large with abundant clear or oxyphilic cytoplasm and large atypical, hyperchromatic nuclei demonstrating irregularity of the nuclear contour and variability of the chromatin distribution, ranging from even to dense
  • Nuclei typically protrude into the gland lumen, giving the cell a hobnail appearance
  • Intraglandular proliferation can be striking, producing a papillary or cribriform pattern
  • Rare mitotic figures can be seen
  • Tissue specimens will often show other features associated with gestation, such as decidual change
  • It is most commonly seen in the upper endocervical canal but can involve glands anywhere in the endocervix
  • Affects superficial or deep glands; tends to be focal, but may be extensive, producing a confluent appearance
  • Five histologic variants reported (Adv Anat Pathol 2002;9:12):
    • Minimal atypia: nuclear enlargement is minimal and occurs in limited foci; usually at the beginning of gestation
    • Early secretory pattern: resembles normal early secretory endometrium with subnuclear or subnuclear / supranuclear vacuoles
    • Secretory or hypersecretory pattern: the classically recognized pattern; glandular cells with intense and diffuse cytoplasmic vacuolization; enlarged and hyperchromatic nuclei are usually pyknotic
    • Regenerative, proliferative or nonsecretory pattern: no or minimal evidence of secretory activity; enlarged nuclei show a vesicular configuration or a granular chromatin with a well delineated nuclear membrane
    • Monstrous cell pattern: usually focal, with giant and bizarre nuclei, which involve all the cells in the glands
Micro Images

Images hosted on PathOut server:

Contributed by Leonel Maldonado, M.D.:

Arias-Stella reaction, 10×

Arias-Stella reaction, 20×



Images hosted on other servers:

Site unspecified

Histology image of endometrium

Cytology Description
  • Arias-Stella reaction is uncommonly seen in Pap smears
  • Often overdiagnosed as SIL, but pregnant women with atypical glandular lesions (AGUS) may have SIL on subsequent biopsy (Acta Cytol 2001;45:294)
  • Characterized by large, pleomorphic cells with large, hyperchromatic, eccentrically located nuclei with fine to granular chromatin and prominent nucleoli (can be multiple)
  • The cytoplasm is abundant and pale, fine to coarsely vacuolated and PAS positive
  • No stratification or crowding occurs
  • Arias-Stella cells are polyploid (but not aneuploid)
  • Mitotic figures and intranuclear cytoplasmic invaginations may be seen
Positive Stains
Negative Stains
  • Wild type p53
Differential Diagnosis